Bone marrow (BM) is accepted as the tissue of choice for the detection of monoclonal populations in leukemias and lymphomas; however, obtaining BM can be painful and traumatic for the patients. Although it is possible to detect clonality in peripheral blood (PB) samples, there are no reports comparing the results observed from BM with those from PB. Lymphoblastic leukemias and lymphomas are derived from B-lymphocytes in 80% of cases. In the early stages of their maturation, the immunoglobulin heavy chain genes (IgH) undergo rearrangements among their V, D, and J segments, giving rise to the Complementarity Determining Regions (CDR). Of these, CDR3 is unique for each lymphocyte and therefore it can be used as a tumour-specific marker in these malignant disorders. Among the 104 patients from whom we obtained pre-treatment paired samples of PB and BM, 94 (90.4%) showed concordant results. Similarly, at the end of treatment, 40 of 44 patients (90.9%) showed this concordance. During treatment only 24 patients were monitored and monoclones disappeared in 12 patients; in the other half, they persisted either partial or totally. We demonstrate that the detection and monitoring of monoclonal populations in the PB, in comparison with BM, was achieved with a statistical sensitivity of 90% and specificity of 92%.